T-Cell lymphoma model for the analysis of interleukin 1-mediated T-cell activation.
Several laboratories have recently demonstrated that the requirement for macrophages in mitogen-induced production of murine T-cell interleukin 2 (IL-2; formerly referred to as "T-cell growth factor") could be circumvented by using the macrophage-derived peptide interleukin 1 (IL-1; formerly referred to as "lymphocyte-activating factor"). Using two cloned T-cell lymphomas, we investigated the mechanism through which IL-1 exerted its effect on IL-2 production. One of the cell lines used (LBRM-33 5A4) produces large concentrations of IL-2 upon mitogen stimulation, whereas the second (LBRM-33 1A5) is incapable of producing IL-2 in response to mitogen. It was observed that addition of purified IL-1 to nonproducer 1A5 cells converted them to a state in which subsequent mitogen stimulation triggered production of IL-2. The concentration of IL-2 produced by IL-1 treated 1A5 cells was equivalent in magnitude to that generated by mitogen-stimulated 5A4 cells (500-1000 units/ml, or approximately 1000 times the concentration of IL-2 contained in conventional preparations of murine mitogen-conditioned medium). The observations that (i) brief exposure to IL-1 was sufficient for 1A5 cell conversion to IL-2 production and (ii) IL-1 could actively be absorbed from culture medium by live or fixed 1A5 cells led us to propose the existence of IL-1 receptors on responsive 1A5 cells. On the basis of these experiments, we have postulated that IL-1 mediates its effect on immune reactivity (enhancement of thymocyte mitogenesis and induction of antibody and cytotoxic T cell responses) by maturation of a subset of immature T cells to the point where they are capable of IL-2 production. Subsequent release of IL-2 after ligand activation allows for clonal expansion of activated T cells which mediate particular effector functions.
D000818:Animals; D002460:Cell Line; D007375:Interleukin-1; D008213:Lymphocyte Activation; D008223:Lymphoma / Q000276:immunology*; D051379:Mice; D008954:Models, Biological; D011506:Proteins / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D007375:Interleukin-1; D011506:Proteins